Idelalisib with Clozapine Interaction Details
Brand Names Associated with Idelalisib
- Idelalisib
- Zydelig®
Brand Names Associated with Clozapine
- Clozapine
- Clozaril®
- FazaClo® ODT
- Versacloz®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 06, 2023
Interaction Effect
Increased clozapine exposure
Interaction Summary
Concomitant use of clozapine (CYP3A4 substrate) and a CYP3A4 inhibitor may lead to increased clozapine levels and increased risk for adverse reactions. If used concomitantly, monitor for adverse reactions and consider clozapine dose reduction as necessary. If this drug is discontinued, monitor for lack of clozapine effectiveness and consider increasing the dose.
Severity
Major
Onset
Unspecified
Evidence
Theoretical
How To Manage Interaction
Concomitant use of clozapine (CYP3A4 substrate) and a CYP3A4 inhibitor may lead to increased clozapine levels and increased risk for adverse reactions. If used concomitantly, monitor for adverse reactions and consider clozapine dose reduction as necessary. If this drug is discontinued, monitor for lack of clozapine effectiveness and consider increasing the dose.
Mechanism Of Interaction
Inhibition of CYP3A4-mediated clozapine metabolism
Literature Reports
A) Concomitant administration of nefazodone may result in decreased clearance resulting in elevated plasma concentrations of clozapine and norclozapine. A 40-year-old man with a history of schizophrenia was successfully treated with clozapine and risperidone for several years. After experiencing persistent negative symptoms, nefazodone was initiated at 200 mg/day for 7 days and then increased to 300 mg/day. Seven days later, the patient reported increased anxiety and dizziness. Physical exam revealed mild hypotension. An increase in plasma concentrations and decrease in clearance of both clozapine and norclozapine was documented. Nefazodone dose was reduced to 200 mg/day and, within 1 week, the patient's symptoms and hypotension resolved. Nefazodone may cause a modest, dose-dependent reduction in the clearance of both clozapine and norclozapine, with resultant increases in serum concentrations. The author suggests that this effect may be due to nefazodone inhibition of the cytochrome P450 3A4 isoenzyme. Caution is suggested when prescribing nefazodone concomitantly with clozapine .
B) Six patients receiving a stable dose of clozapine for at least 2 weeks were selected to begin nefazodone therapy at 100 mg twice daily for 1 week and then 200 mg daily for 2 more weeks. The overall changes in clozapine pharmacokinetics were minimal when nefazodone was coadministered. Clozapine concentrations increased by an average of 19 mcg/L (4% of baseline) and norclozapine concentrations increased by 46 mcg/L (16% of baseline). Cytochrome P450 3A4 (CYP3A4) has been postulated to play a significant role in the metabolism of clozapine. Nefazodone is an inhibitor of CYP3A4. Because this study failed to show a significant interaction between these 2 drugs, CYP3A4 may play only an insignificant role in the metabolism of clozapine, or alternative routes of metabolism may be activated when CYP3A4 is inhibited .
Idelalisib Overview
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Idelalisib is used along with another medication rituximab (Rituxan) to treat chronic lymphocytic leukemia (CLL; a type of cancer that begins in the white blood cells) in people whose cancer came back after receiving other cancer treatments. It is also used to treat certain types of follicular lymphoma (FL; a type of cancer that begins in the white blood cells) and small lymphocytic lymphoma (SLL:a type of cancer that begins in the white blood cells) in people whose cancer came back after being treated with at least 2 other cancer treatments. Idelalisib is in a class of medications called kinase inhibitors. It works by blocking the action of the abnormal protein that signals cancer cells to multiply. This helps stop the spread of cancer cells.
Clozapine Overview
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Clozapine is used to treat the symptoms of schizophrenia (a mental illness that causes disturbed or unusual thinking, loss of interest in life, and strong or inappropriate emotions) in people who have not been helped by other medications or who have tried to kill themselves and are likely to try to kill or harm themselves again. Clozapine is in a class of medications called atypical antipsychotics. It works by changing the activity of certain natural substances in the brain.
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Definitions
Severity Categories
Contraindicated
These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.
Major
This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.
Moderate
This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.
Minor
While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.
Onset
Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.
Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.
Evidence
Level of documentation of the interaction.
Established: The interaction is documented and substantiated in peer-reviewed medical literature.
Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.
How To Manage The Interaction
Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.
It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.
Mechanism Of Interaction
The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.
Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.
Where Does Our Information Come From?
Information for our drug interactions is compiled from several drug compendia, including:
The prescribing information for each drug, as published on DailyMED, is also used.
Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.
The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.